On 17 November 1996, Sanjeev won her first ITF Women's Circuit title, defeating Raluca Sandu in the finals of the $25,000 tournament in Bad Gögging, Germany.

Nirupama shifted her base to Sarasota, Florida in 1997 where she trained with David O Meara who was the former coach of Leander Paes for two years.

A month later, she competed in the main draw of a WTA-level event for the first time (at the 1997 Japan Open), with qualifying wins over Yi Jing-qian, Keiko Nagatomi, and Akiko Morigami.

During the clay court season, she would fall in the first qualifying matches of both the Internationaux de Strasbourg (to Kristina Brandi), as well as Roland Garros (to Park Sung-hee).

She became the first Indian female in the modern era to feature and win a round at a main draw Grand Slam, beating Italy's Gloria Pizzichini.

Earlier in the 2000, she won her second (and ultimately the last) ITF title in April, winning against Sai Jayalakshmy Jayaram in the $10,000 tournament held on carpet courts in New Delhi.

However, she won her first (and eventually, the only) main draw doubles match of a Grand Slam at the 2001 Wimbledon Championships, partnering Rika Hiraki; the pair had defeated Silvia Farina Elia and Iroda Tulyaganova.

She won the last two ITF doubles titles of her career in April 2001; one in Ho Chi Minh City (with Manisha Malhotra) and one in Sarasota, Florida (with Melissa Middleton).

She went into her first retirement from the sport, losing in the second qualifying round of the ITF $50,000 tournament in Louisville, Kentucky to Petra Rampre, in late-July 2003.

Playing in her first match in six years, she beat Tamara Čurović before losing to Tamarine Tanasugarn in the second round of the ITF $50,000 NECC–ITF Women's Tennis Championships in November, at Pune.

After defeating Sarah Borwell and Anna Smith (England) in the quarterfinals alongside Poojashree Venkatesha, they lost to Australia's Olivia Rogowska and Jessica Moore in the semifinals, thereby sending them into the bronze-medal playoff.

In the mixed doubles event, she partnered Rohan Bopanna but was defeated in the pre-quarterfinals by Anastasia Rodionova and Paul Hanley (Australia).

Partnering Tara Iyer in women's doubles, she lost in round two to the Chinese team of Sun Shengnan and Zhang Shuai.

For the past five years, Nirupama has been on the expert commentary team along with Indian tennis legend Vijay Amritraj for ESPN-STAR sports.